New liquid crystal polycarbonate micelles for intracellular delivery of anticancer drugs.

ABSTRACT

To construct pH/temperature dual sensitive micelles as novel drug delivery carriers, the synthesis of two diblock copolymers mPEG113-PMCC9-(PMCC-DBO)27 and mPEG43-PMCC25-(PMCC-DHO)15 based on mPEG and polycarbonate modified by acid and liquid crystal groups is described. In aqueous solution, mPEG113-PMCC9-(PMCC-DBO)27 and mPEG43-PMCC25-(PMCC-DHO)15 could self-assemble to form nanospheres and vesicles at very low critical micelle concentration, respectively. Both nanospheres and vesicles were less than 100 nm in diameter and demonstrated high loading capacity of doxorubicin (DOX) through ionic interaction between the free carboxyl groups in PMCC segments and the amine groups in DOX. In vitro release studies indicated that the two copolymer micelles were capable of pH/temperature-triggered release of doxorubicin and without a significant initial burst release. Furthermore, MTT assays showed that the blank copolymer micelles were nontoxic, while the drug-loaded micelles exhibited potent cytotoxic activity towards HeLa cells. These pH/temperature responsive copolymer micelles provided a new strategy for constructing stimuli-responsive drug delivery carriers in chemotherapy.